A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer: The MONAVI - GINECO study.
Aniline Compounds
Carcinoma, Ovarian Epithelial
/ drug therapy
Female
Humans
Myeloid Cell Leukemia Sequence 1 Protein
/ therapeutic use
Neoplasm Recurrence, Local
/ pathology
Ovarian Neoplasms
/ pathology
Platinum
/ therapeutic use
Prospective Studies
Proto-Oncogene Proteins c-bcl-2
Sulfonamides
Thrombocytopenia
BH3 mimetics
Early phase study
Ovarian cancer
Platinum resistance
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
22
11
2021
revised:
14
01
2022
accepted:
16
01
2022
pubmed:
7
2
2022
medline:
27
4
2022
entrez:
6
2
2022
Statut:
ppublish
Résumé
There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-x We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (<G3). Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned. The 3-month PFS was 22.7% [ Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity. Clinicaltrials.gov identifier: NCT02591095.
Sections du résumé
BACKGROUND
There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-x
METHODS
We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (<G3). Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned.
RESULTS
The 3-month PFS was 22.7% [
CONCLUSIONS
Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity.
TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT02591095.
Identifiants
pubmed: 35123771
pii: S0090-8258(22)00048-8
doi: 10.1016/j.ygyno.2022.01.021
pii:
doi:
Substances chimiques
Aniline Compounds
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Proto-Oncogene Proteins c-bcl-2
0
Sulfonamides
0
Platinum
49DFR088MY
navitoclax
XKJ5VVK2WD
Banques de données
ClinicalTrials.gov
['NCT02591095']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
30-39Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest F. Joly: Abbvie for Navitoclax provision, consulting for Roche, GSK, Astra Zeneca, Clovis, MSD, Ipsen, Janssen, Astellas, Pfizer, Sanofi, BMS, Bayer. M. Fabbro: Consulting for GSK, Astra-Zeneca, and Clovis Oncology. P. Follana: GSK, Astra Zeneca, Clovis, MSD, Novartis, DAIICHI. J.S. Frenel: Consulting for Novartis, Pfizer, Astra Zeneca, Lilly, Roche, BIOCAD, DAIICHI, GSK-Tesaro, Pierre Fabre, and Clovis oncology. B.You: Consulting for MSD, Astra-Zeneca, GSK-TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, and Myriad. J. Lequesne, J. Medioni, A. Lesoin, S. Abadie-Lacourtoisie, A. Floquet, L. Gladieff, C. Gavoille, E. Kalbacher, M. Briand, P.E. Brachet, F. Giffard, L-B. Weiswald, P.A. Just, C. Blanc-Fournier, A. Leconte, B. Clarisse, A. Leary, L. Poulain: no conflicts of interest to disclose in relation with this work.